Abstract

Background

Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA) may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomised controlled trials.

Objectives

To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people.

Selection criteria

Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials.

Data collection and analysis

The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat basis, and summarised narratively information on safety and adherence.

Main results

Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up.

In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome.

None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention); MD -0.07 (95% CI -0.25 to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies.

The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15% of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality.

Authors' conclusions

Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems.

Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.

Plain language summary

Fish oils for the prevention of dementia in older people

Dementia is a progressive illness which mainly affects older people. Previous research from observational studies has suggested that increased consumption of fish oils rich in omega-3 long-chain polyunsaturated fatty acids (omega-3 PUFA) may reduce the chance of developing dementia, while other studies show no effect. Oily fish, such as salmon, mackerel, herring and sardines are a rich source of omega-3 PUFA which are essential for brain development.

The authors of this review included studies where healthy participants over the age of 60 years who were cognitively healthy at the start of the study were randomly assigned to receive extra omega-3 PUFA in their diet or a placebo (such as olive oil). The main outcomes of interest were new cases of dementia diagnosed during the study period, cognitive decline, side-effects, and adherence to the intervention.

The authors included three randomised controlled trials involving 3536 participants. In two studies participants were randomly assigned to receive gel capsules containing omega-3 PUFA or olive or sunflower oil for six or 24 months. In the third study, participants were randomly assigned to receive tubs of margarine spread for 40 months (regular margarine versus margarine fortified with omega-3 PUFA).

None of the studies examined the effect of omega-3 PUFA on new dementia cases over the study period. In two studies involving 3221 participants there was no difference between the omega-3 PUFA and placebo group in mini-mental state examination score at final follow-up. In two studies (1043 participants), other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced little or no cognitive decline during the studies.

The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems, but overall minor symptoms were reported by fewer than 15% of participants, and people in the control group were just as likely to report symptoms as those receiving an omega-3 PUFA supplement. Adherence to the supplementation protocol was high in all trials with on average over 90% of supplements being apparently consumed by trial participants. All three studies included in this review were of high methodological quality, and so the findings are unlikely to be due to chance or bias.

The results of the available studies show no benefit for cognitive function with omega-3 PUFA supplementation among cognitively healthy older people. Omega-3 PUFA supplements may have other health benefits, and the authors comment that consumption of fish is recommended as part of a healthy diet.

Longer studies are required, during which greater changes in cognitive function may occur, to enable researchers to identify possible benefits of omega-3 PUFA in preventing cognitive decline.

平易な要約

高齢者での認知症予防に対する魚油

認知症とは、主に高齢者が罹病する進行性疾患である。これまでの観察研究による研究では、オメガ3長鎖多価不飽和脂肪酸（オメガ3PUFA）に富んだ魚油を多く摂ると、認知症の発症率が低下すると示唆されてきたが、効果を示さないとする他の研究もみられる。鮭、鯖、鰊、鰯などの魚油は、脳の発達に必須であるオメガ3PUFAに富んだ食品源である。レビューアらは、研究開始時に認知機能が正常の60歳超の正常参加者の食事にオメガ3PUFAを添付するか、またはプラセボ（オリーブ油など）にランダムに割り付けた研究を選択した。評価対象とした主要アウトカムは、試験実施中に診断された認知症の新規発症、認知機能低下、副作用、介入の服薬継続率であった。レビューアらは、3,536名の参加者を対象とした3件のランダム化比較試験を選択した。2件の研究では、参加者は6～24ヵ月間オメガ3PUFAまたはオリーブ油／ひまわり油の入ったゲルカプセルの投与にランダムに割り付けられた。3件目の研究では、参加者は40ヵ月間（パンに）マーガリン塗布（普通のマーガリン対オメガ3PUFA強化マーガリン）にランダムに割り付けられた。試験実施中の認知症の新規発症に対するオメガ3PUFAの効果を検討した研究はなかった。3,221名の参加者を対象とした2件の研究では、最終追跡時のMini-Mental State Examinationスコアに関して、オメガ3PUFA群とプラセボ群とに差はなかった。1,043名の参加者を対象とした2件の研究によると、単語学習、数唱、言語流暢性などの認知機能の他の検査では、オメガ3PUFA補充に有益な効果が認められなかった。介入群とコントロール群の参加者はどちらも、研究中にほとんどあるいはまったく認知機能低下の発現がなかった。オメガ3PUFA補充で主に報告された副作用は、軽度の胃腸障害であったが、軽微な症状は全体として参加者の15%未満から報告があり、コントロール群における報告率もオメガ3PUFA補充者と同程度であった。補充プロトコルの服薬継続率はすべての試験で高く、試験参加者による摂取は平均して約90%超であった。本レビューに選択した3件の研究は方法論的に質がすべて高く、得られた所見が偶然またはバイアスによる可能性は低かった。得られた研究の結果では、認知機能が正常の高齢者における認知機能に対しオメガ3PUFA補充による利益は認められなかった。オメガ3PUFA補充ではその他にも健康上の利益がみられる可能性があり、魚の摂取は健康的な食事の一部として推奨される。期間中に認知機能のより大きな変化を見るにはもっと長期の研究が必要であり、それによって研究者には認知機能低下の予防におけるオメガ3PUFAで推定される利益が同定できると考えられる。